Defining and Predicting HIV Immunological Non-Response: A Multi-Definition Analysis from an Indonesian Cohort

Immunological non-response (INR) to antiretroviral therapy (ART) is a critical concern for PLHIV, characterized by inadequate CD4⁺ T-cell recovery despite virological suppression. This retrospective study analyzed medical records of virologically suppressed adult PLHIV on ART (2004-2024) at two hospitals in Surabaya, Indonesia, using four operational categories to identify clinical and demographic determinants of INR. Patients were classified as immunological responders (IRs) or non-responders (INRs) based on four definitions: INR1 (CD4⁺ gain < 100 cells/mm³), INR2 (CD4⁺ < 350 cells/mm³), INR3 (meeting of either criterion), and INR4 (meeting of both criteria). Of 464 patients, 382 were analyzed. Baseline CD4⁺ < 200 cells/mm³ strongly predicted INR2 (aOR = 5.60, 95% CI: 2.95-10.62) and INR3 (aOR = 4.46, 95% CI: 2.39-8.29), while anal sexual transmission was protective against INR2 (aOR = 0.42, 95% CI: 0.19-0.92) and INR3 (aOR = 0.41, 95% CI: 0.19-0.89). By month 12, IR groups had over 350 CD4⁺ cells/mm³, with faster recovery slopes in months 0-6 (IR: >20 vs. INR: <10 cells/mm³/month). INR1 and INR4 had flat or negative slopes at 12-24 months, while IR groups had positive slopes. Baseline CD4⁺ was the strongest INR predictor, suggesting the value of early ART and individualized care for Indonesian PLHIV.